Bone Marrow Stem Cells as a Vehicle for Delivery of Heme Oxygenase-1 Gene

Bone marrow-derived mesenchymal stem cells (MSCs) are readily accessible adult stem cells that are capable of self-renewal and multilineage differentiation. Human MSCs have been well described and used in xenogenic models for investigation, but rodent MSCs, if available, would eliminate problems associated with transplantation across a species barrier. Here we describe an effective method to generate rat MSCs and use these cells to target gene delivery in vivo. MSCs that were capable of retaining their differentiation potential after several population doublings in culture were generated from rat bone marrow. Marrow-derived MSCs were enriched and infected with an adenoviral vector carrying the heme oxygenase gene (Ad5/HO-1). Transfected rodent MSCs retained their differentiation potential, even after 10 passages, as determined by their ability to differentiate into adipocytes. Western analyses clearly indicated that Ad5/HO-1-transfected rodent MSCs exhibited increased HO-1 expression. Trafficking of fluorescent rat MSCs was evaluated 24 and 48 h after MSC infusion. Most of the infused cells accumulated in the lungs of recipients where they expressed HO-1. Thus, bone marrow-derived MSCs are useful for gene delivery replacement of the products of deficient genes. These cells may be useful for potentiation of wound healing because they retain their pluripotential differentiation ability.